Four investigators will continue to study the biology, genetics, and biochemistry of lymphoid and other cells which participate in the immune response. Whenever possible, continuous cloned cell lines will be used and somatic cell genetic and biochemical techniques will be employed to study the properties and products of these cells. In collaborative studies Drs. Nathenson and Scharff are attempting to generate hybridomas making homogeneous antibodies against H-2 and other surface antigens; Drs. Birshtein and Scharff continue to examine the regulation and structure of immunoglobulin genes by isolating and characterizing mutant mouse myeloma cells, and Drs. Bloom and Scharff have established and characterized a series of hybrid macrophage-like cell lines that can carry out a wider variety of biological activities than the transformed cell lines previously available. In addition, the individual investigators hope to determine if the somatic generation of antigen binding diversity in mouse myeloma cells is due to changes in the sequence of the hyper-variable regions: to determine the detailed sequence of some H-2 moleccles and of naturally occurring mutants in the H-2 molecule which cause MLC reactions; to isolate mutant cell lines in a variety of macrophage functions: to develop in vitro systems to study the immune response and genetic restrictions in human cells; and to characterize mutant immunoglobulins in order to elucidate the organization of immunoglobulin genes.